Generally, drugs administered for the purpose of medical treatment or diagnosis once go through the systemic blood circulation, and then take the process of absorption, distribution, metabolism, excretion and the like. In the process of absorption and distribution, the drug moves along on flow of the blood, while it transfers to each spaces of intravascular, interstice and intracellular by diffusion and transportation of a free drug being in the state of unbound form with proteins, and finally the drug arrives at the active region of target. When movement of the drug reaches a steady state, then the free drug concentration in each space become uniform, thus the whole pattern of the concentration of the drug is determined by the binding level with proteins. Hence, in accordance with the property, a drug in vivo, may partially exists in the form of reversible binding state with biopolymers such as plasma proteins. Generally, drugs permeable through capillary wall or cell membrane are free drugs, therefore, the transfer of such free drugs being unbound with plasma proteins to the active region of target may be greatly influenced by the binding level with plasma proteins.
For example, mercaptoacetylglycylglycylglycine labeled with 99m-technetium (99mTc-MAG3) is widely used in renal scintigraphy, especially the renal plasma flow can be effectively exhibited by its efficient renal extraction and renal tubular secretion. It is known that about 90% of 99mTc-MAG3 binds to plasma protein in an ordinary clinical dose (Bubeck B. et al., J. Nucl. Med., 31, 1285–1295, 1990). If the binding of 99mTc-MAG3 with plasma protein is inhibited by drugs having high binding affinity to the same binding site on protein with 99mTc-MAG3, then more clear renal imaging can be obtained in the earlier stage after the administration, thus it may be thought that the dose of radioactivity to the patient can be reduced at the same time.
On the contrary, if the binding of drugs with plasma protein is increased, then the concentration of the free drugs in the blood can be kept in lower level for long period, therefore, it may be possible to achieve continuous appearance of pharmacological effects.
However, at the present stage, little is known as the research work for improving therapeutic effect or diagnostic effect of the drugs by regulating the concentrations of the free drugs, using the binding affinity of the second drug with plasma proteins.